IDEAYA Reports 6.9-Month PFS, 37.1% ORR in mUM Trial; NDA Filing Underway
IDYA•Darovasertib plus crizotinib extended median PFS to 6.9 months versus 3.1 months in first-line HLA*A2:01 negative metastatic uveal melanoma (HR 0.42), reducing progression risk by 58%. The combo achieved 37.1% ORR and 73.3% DCR with a 9.2% TR-SAE rate, and NDA filing is underway under RTOR.
1. OptimUM-02 Trial Design and Primary Results
The global Phase 2/3 OptimUM-02 trial randomized 313 HLA*A2:01 negative metastatic uveal melanoma patients 2:1 to darovasertib plus crizotinib or investigator’s choice therapy, demonstrating median progression-free survival of 6.9 months versus 3.1 months by blinded independent central review (HR 0.42; p<0.0001).
2. Response Rates and Disease Control
The darovasertib combination achieved a 37.1% overall response rate and 73.3% disease control rate by blinded review, compared with 5.8% ORR and 31.1% DCR in the control arm, with a median duration of response of 6.8 months.
3. Safety and Tolerability
The regimen exhibited a manageable safety profile, with 40.6% Grade 3/4 treatment-related adverse events, 9.2% treatment-related serious adverse events, and low discontinuation rates for darovasertib (2.5%) and crizotinib (10%).
4. NDA Submission under RTOR and Next Steps
An NDA submission under the FDA’s Real-time Oncology Review program is in progress, with IDEAYA targeting completion in H2 2026 and planning a pre-specified interim analysis for overall survival data to support potential full approval.
